Method and apparatus for treatment of viral diseases

ABSTRACT

An apparatus and method for treating viral infections delivers electrical stimulation to the skin or mucosa of a patient. The electrical stimulation is applied as a series of electrical pulses having different electrical characteristics. The apparatus may include a housing having at least two electrodes supplied with both AC and DC voltage, and powered by a battery. The electrodes are designed so as to maximize contact with the patient.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/855,917, filed Sep. 14, 2007, which is a continuation of U.S. patentapplication Ser. No. 10/624,816, filed Jul. 22, 2003 and issued Sep. 18,2007 as U.S. Pat. No. 7,272,440, which is a continuation of U.S. patentapplication Ser. No. 09/727,287, filed Nov. 29, 2000 and issued on Sep.9, 2003 as U.S. Pat. No. 6,618,625. The disclosures of all of theabove-referenced prior applications, publications, and patents areconsidered part of the disclosure of this application, and areincorporated by reference herein in their entirety.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to a method and apparatus for deliveringelectrical stimulation to pathological tissue, and more particularly, totreating viral infections by applying a series of electrical pulseshaving different maximum amplitudes to the affected skin or mucosa.

2. Description of the Related Art

Viruses are the smallest infectious agents and contain a molecule ofnucleic acid (RNA or DNA) as their genome. Nucleic acid is enclosed in aprotein shell. The viral nucleic acid contains information necessary forprogramming the infected host cell to synthesize the specific number ofmacromolecules. Toward the end of the replicative cycle, more viralnucleic acids and coat proteins are produced. The coat proteins assembletogether to form the symmetrical protein shell which encloses thenucleic acid genome.

There are eight identified herpes viruses that have been associated withhuman disease conditions. The alpha-herpes viruses, HSV-1, HSV-2, andVZV-2, known as oral herpes, genital herpes, and herpes zosterrespectively, are neurotropic since they actively infect nervous tissue.Five other herpes viruses are lymphotropic since they replicate in thelymphatic system. These include HCMV (human cytomegalovirus), HHV-6,HHV-7, HHV-8 (KHSV) and EBV. HHV-6 has been associated with multiplesclerosis. HHV-8 (KHSV) and EBV have been linked to the human cancersKaposi's sarcoma and Epstein-Barr disease.

Disease states are also caused by a variety of other viruses. Viralhepatitus is a serious liver disease of particular concern forhealthcare professionals. One form of hepatitus, hepatitus C, isconsidered responsible for approximately 10,000 deaths per year. Thehuman papilomavirus (HPV) is responsible for most of the cervicalcancers worldwide, genital warts and the formation of verrucae, wartsthat form on the soles of the feet. HPV has also been associated withseveral oral cancers. In addition, the HIV virus has killed more than 19million people and infected 34 million more, causing an epidemic thatwill continue to devastate communities around the world.

Oral Herpes The HSV-1 Virus

Herpes simplex virus (HSV) infections of the oral tissues are among themost common infectious illnesses involving man. Both primary (initial)and recurrent forms of the infection occur, these being referred to asacute primary herpetic gingivo stomatitis, and recurrent herpeslabialis. Although oral herpes infections may be considered primarilynuisance diseases, gingivo stomatitis can be a very painful anddebilitating illness, while recurrent oral herpes in immunosuppressedsubjects may be severe and even life-threatening (Overall, 1979; Ho,1979; Faden et al, 1977).

The vast majority of oral herpes infections are caused by the HSV type 1strain. There are no precise data for the frequency of oral herpesinfections. It is estimated that there are about 500,000 cases of herpesstomatitis each year in the U.S. Recurrent herpes labialis occurs inapproximately one-third of the population and the mean number ofepisodes per year in individuals with recurrent disease is 1.6 (Overall,1979). This projects at about 100 million episodes of herpes labialis inthe U.S. each year.

There are several factors that contribute to the significance of oralherpes infections. First, herpes gingivo stomatitis can be a severeillness. Fever, toxicity, and exquisitely painful mouth lesions mayinterfere with fluid intake and require hospitalization for intravenousfluids. Second, frequent recurrent lesions of the lips are of cosmeticconcern, particularly in females. Third, cold sores may be the source ofHSV for transmission to immunosuppressed or other hospitalized patients.Fourth, oral herpes in the immunosuppressed patient is often a severe,life-threatening disease. Finally, there is currently no satisfactoryand effective form of therapy for either primary or recurrentmucocutaneous HSV disease in the normal host.

Most patients develop vesicles within 12 hours, which rupture to formulcers or crusts in 36 to 48 hours. Most patients lose the crust andhave healed ulcers by day 8 to 10. Results from clinical trials onrecurrent herpes labialis has shown that about 25% of patients hadepisodes one or more times a month, almost two-thirds had one episodeevery 2-4 months, and less than 25% had an episode less often than every4 months (Spraunce et al, 1977).

Genital Herpes The HSV-2 Virus

Despite the emphasis and publicity on safe sex to prevent AIDS, a recentstudy by the Centers for Disease Control has shown that genital herpeshas increased fivefold among white teenagers since the late 1970's, anddoubled among whites in their 20's (New Eng. J. of Medicine, Oct. 16,1997). One in five Americans over the age of 12 years carries the virusthat causes genital herpes, with 500,000 new cases occurring each year.

It is currently standard practice in the U.S. to perform Cesareandelivery on pregnant women with recurrent herpes to reduce the risk oftransmission of the virus to newborns (J. Obstetrics & Gynecology,October 1996). In spite of this, 20-30% of all infants born via Cesareandelivery still have the herpes virus. More than 40% of newborns infectedwith HSV die or suffer neurologic impairment. What exacerbates thisproblem is that women are 45% more likely to be infected with HSV-2 thanmen. Since there has been a dramatic increase in genital herpes amongthe younger generations, it means that a substantial number of womenentering their childbearing years are infected with HSV-2, or are atrisk of contracting infection. Despite antiviral therapy, neonatalherpes is still a major life threatening infection.

After inoculation and limited replication at genital sites, HSV-2ascends along neuronal axons to establish latent infection in thelumbosacral ganglia. During this initial phase, infectious virus is,present at genital sites for days or weeks, usually without lesions.When a new cycle of viral replication is triggered, reactivation occursand infectious virus is delivered back down the neural pathways to themucosa or skin. The return of infectious virus to genital sites duringHSV-2 reactivation rarely causes any symptoms. HSV-2 is a chronic,persistent infection that causes subclinical reaction in about 1% ofinfected persons. Since about 45-50 million people in the U.S. areinfected, HSV-2 can spread efficiently and silently through thepopulation. People who have sexual contact with many partners willfrequently have exposure to an infected person who is shedding HSV-2. Asthe overall prevalence of HSV-2 infection continues to rise, contactwith fewer partners will permit exposure.

The concept that HSV persists in the nuclei of cells in the sensoryganglia suggests that any topical treatment will be ineffective indestroying the virus in these hidden locations. About 25 viruses havebeen placed in the HSV group and they all contain a core of doublestranded DNA surrounded by a protein coat that exhibits isocahedrilsymmetry. This in turn is enclosed in an envelope which containsessential lipids. The structural proteins of herpes simplex virusinclude nine polypeptides which have been found in the enveloped virion,two polypeptides which are associated with the envelope, two argininepolypeptides within the virus core, as well as guanine and cytosine. Thevirus enters the cell either by fusion with the cell membrane or bypinocytosis. It is then uncoated and the DNA becomes associated with thenucleus. Soon after infection the virus codes for its own DNA polymeraseand other enzymes such as thymidine kinase which is associated with theDNA replication.

A variety of treatments have been used for genital herpes but none isentirely satisfactory. No satisfactory vaccine has been found. Insuperficial infections, topical agents such as Idoxuridine,Trifluorothymidine, or Acyclovir are sometimes effective. The drug ofchoice for the treatment of herpes simplex is Acyclovir which is theonly FDA approved drug. Sales of Zovirax® (Burroughs Wellcome) weregiven at about $500M. Annual estimated sales for this product exceeded$2 billion worldwide in 1997. Administered orally for systemicabsorption, Acyclovir is limited by several factors:

-   -   1) side effects include rash, nausea, vomiting, diarrhea, or        pain, burning or itching at the site where the drug is applied,        anorexia and possible eye injuries.    -   2) cost; the average annual cost to a patient is around $1000.    -   3) emergence of drug-resistant virus strains.    -   4) presence of a large number of “early reactivation” patients        for whom Acyclovir does not work.    -   5) a 6-10 day treatment cycle; patients with HSV-1 (oral        herpes/cold sores) must decide if treatment is worth 6-10 days        use of an expensive systemic drug with potential side effects.

First episodes of the virus should all be treated as early as possiblewith one of three available oral antiviral agents. Effective treatmentsinclude: Acyclovir (Zovirax™) where the usual dose is 200 mg five timesdaily. Valacyclovir HCl (Valtrex™) is an improved oral formulation ofAcyclovir which requires less frequent dosing at 500 mg twice daily.Famciclovir (Famvir™) is the oral formulation of penciclovir and it isdosed for primary infections at 250 mg three times daily. Studies haveproven all three drugs to be equally effective. In North America, firstepisode treatment is generally prescribed for 10 days, but in Europe andthe UK, treatment is generally prescribed for 5 days. These antiviralmedications can be taken orally very early in a recurrent episode.

Herpes Zoster

Herpes zoster, also known as shingles, is due to invasion of posteriorroot ganglia by the causative virus and is characterized by severe painfollowed by a rash over cutaneous distribution of the affected nerve.The virus, varicella-zoster (VZ), causes two diseases, varicella(chickenpox) resulting from the first exposure to the virus inchildhood, and zoster, a secondary infection due to reactivation of thelatent VZ virus. Shingles is a painful and potentially debilitatingdisease that affects 750,000 people each year in the U.S. The conditionis most commonly experienced by older Americans and is caused by areactivation of the varicella-zoster virus, the same herpes virus whichcauses chickenpox. A major challenge for physicians in managing patientswith shingles is alleviating the severe pain associated with an activeshingles rash, as well as postherpetic neuralgia (long-term debilitatingpain) which may occur following rash healing.

Herpes and Multiple Sclerosis

A strain of reactivated herpes virus may be associated with multiplesclerosis (MS), an autoimmune disorder in which the body attacks its owntissues. Results of a study conducted by scientists at the NationalInstitute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md.,add to mounting evidence of the role of viral triggers in MS and mayserve as the cornerstone for clinical trials using antiherpetic agentsas a treatment. This is the first published large-scale study suggestingan association of a human herpes virus in the disease process of MS. Inthe study, more than 70 percent of patients with the relapsing-remittingform of MS showed an increased immune response to human herpes virus-6(HHV-6) and approximately 35 percent of all MS patients studied haddetectable levels of active HHV-6 in their serum. Scientists believethat there may be a point in time during the progression of MS when thevirus, which lies dormant in the body for years, reactivates, accountingfor its presence in a subset of MS patients. The study appears in theDecember 1997 issue of Nature Medicine.

As many as 350,000 Americans are affected by MS, which is most oftendiagnosed in patients between the ages of 20 and 40 and is characterizedby muscle weakness, visual disturbances, and a variety of otherneurological impairments. The array and severity of symptoms varieswidely from patient to patient and women are more likely to be affectedthan men. The most common form of MS is the relapsing-remitting type. Inthis type of MS, new symptoms appear or existing ones become moresevere, followed by periods of partial or total recovery. Theseflare-ups of new or intensified symptoms last for variable amounts oftime. A second form of MS is a chronic and progressive one in whichsymptoms steadily worsen. HHV-6 is relatively new to scientists and isknown to cause a common childhood illness, roseola. HHV-6 is known to bepresent in 90 percent of the adult American population as a result ofinfection during the first few years of life. Scientists believe thatthe reactivation of HHV-6 virus may be associated with the breakdown ofthe protective covering of nerves, called myelin. Reactivation ischaracteristic of herpes viruses. In the study, investigators screenedthe serum of 102 individuals, 36 of whom had MS. Of the 22 individualswith the relapsing-remitting form of MS, 73 percent had an increase inimmune response to an early antigen of HHV-6, compared to only 18percent of those participants who served as normal volunteers. Inaddition, the scientists detected HHV-6 DNA in the serum (a marker ofactive virus infection) of 15 of 50 individuals with MS. All 47individuals without MS tested negative for the presence of active HHV-6viral infection.

Human Papillomavirus

Human papillomavirus (HPV) is one of the most common sexuallytransmitted diseases. Genital HPV infections are widespread amongsexually active adults. It is estimated that as many as 40 millionAmericans are infected with HPV, and the incidence of the diseaseappears to be increasing. More than 1000 types of HPV have beenidentified. Some cause common skin warts. Others are spread throughsexual contact and result in genital warts.

HPV often results in an infection without any visible symptoms. Thus,individuals may not be aware of the infection or of the potential riskof transmission to others. Genital warts are spread by sexual contactand are highly contagious. Approximately two-thirds of people who havesexual contact with a partner with genital warts will develop warts,usually within about three months of contact.

In women, the warts occur on the outside and inside of the vagina, onthe cervix, and around the anus. In men, the warts occur on the penis,scrotum, and around the anus. Genital warts often occur in clusters, andcan be very tiny or can occur in large masses. Treatment includes theapplication of trichloracetic acid or podophyllin solution. Warts can beremoved by cryosurgery, electrocautery or surgery. Although eliminationof the warts is possible, the viral infection persists and warts oftenreappear after treatment.

To date, there are very few satisfactory treatments, vaccines, or curesfor viral infection. Drug treatments, either topical or ingested, haveshown generally limited benefits. As an alternative to thepharmaceutical approach, the electrical stimulation of infected tissueshas been explored. These methods involve the application of electrodesto the skin near the infected region. Some examples are provided by U.S.Pat. No. 4,913,148 to Diethelm, U.S. Pat. No. 5,133,352 to Lathrop, etal., and U.S. Pat. No. 5,607,461 to Lathrop. The disclosures of each ofthese patents is hereby incorporated by reference in their entireties.Although this technique shows promise, to date, the devices andstimulation protocols used have been less successful at eliminatingviral infection than was hoped.

SUMMARY OF THE INVENTION

The invention includes methods of treating viral infections. In oneembodiment, such a method comprises a treatment protocol including theapplication of a series of pulses of electrical stimulation to apatient's skin or mucosa, wherein the pulses of electrical stimulationhave varying characteristics over the course of the treatment protocol.The pulses may differ in amplitude or frequency. They may alternatebetween AC pulses and DC pulses.

Apparatus for applying electrical stimulation to treat physiological andpathological conditions such as viral infections is also provided. Inone embodiment, the apparatus comprises at least two electrodes and acircuit configured to supply both AC and DC voltage to the electrodes.Other apparatus embodiments include counters for displaying the numberof treatments applied. Still other embodiments include replaceable anddisposable cartridges comprising electrodes and a battery. The batterymay be rechargeable with an external charger. A wide variety ofrechargeable/disposable batteries are commercially available withdifferent form factors, costs, etc.

Advantageous electrode designs for the apparatus are also provided. Inone embodiment, the electrode comprise an elongated surface forapplication to the subject's skin or mucosa.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of one embodiment of an electricalstimulation device.

FIG. 2 is a block diagram of an electrical circuit which is provided insome advantageous embodiments of the stimulation devices of the presentinvention.

FIG. 3 is a perspective view of another embodiment of an electricalstimulation device.

FIG. 4 is a perspective view of another embodiment of an electricalstimulation device.

FIGS. 5A and 5B are side views of another embodiment of the electricalstimulation device, showing the disposable activator inserted into, andremoved from, the housing.

FIG. 5C is an end view of the distal end of the device of FIGS. 5A and5B, showing the position of the electrodes.

FIGS. 6A and 6B are side views of yet another embodiment of theelectrical stimulation device, showing the disposable activator insertedinto, and removed from, the housing.

FIG. 6C is an end view of the distal end of the device of FIGS. 6A and6B, showing the position of the electrodes.

FIG. 7 is a flow chart of an electrical stimulation treatment protocolin accordance with one embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Embodiments of the invention will now be described with reference to theaccompanying Figures, wherein like numerals refer to like elementsthroughout. The terminology used in the description presented herein isnot intended to be interpreted in any limited or restrictive manner,simply because it is being utilized in conjunction with a detaileddescription of certain specific embodiments of the invention.Furthermore, embodiments of the invention may include several novelfeatures, no single one of which is solely responsible for its desirableattributes or which is essential to practicing the inventions hereindescribed.

Referring now to FIG. 1, there is shown one embodiment of the electricalstimulation device of the present invention, useful for treating viralinfections. The device 10 includes a housing 12, which is designed tofit comfortably in the hand of the user. At one end, two electrodes 18 aand 18 b are mounted. The electrodes 18 a, 18 b, have an elongatedsurface for application to the user's skin. The elongated electrodesallow for larger electrode to skin surface contact. As shown in FIG. 1,each electrode 18 a, 18 b may comprise a closed contour. In someembodiments, the electrodes 18 a, 18 b are concentric closed contours.In the embodiment of FIG. 1, the electrodes comprise circuit tracesplated onto a printed circuit board 19 that is attached to one end ofthe housing 12.

It will be appreciated that the electrodes may take many forms andshapes. The electrodes 18 a and 18 b can be oval or elliptical as shownin FIG. 1, rectangular as shown in FIG. 3, or circular, as shown FIG. 4.They may also be square, or any other desired shape, and are preferablygold plated. However, any electrically conductive material can be used.An on/off button or switch 20 that is manually operated is located onthe device, which also can include a first LED 22 that is activated whenthe device is turned on, and a second LED 23 that indicates a lowbattery condition. An alphanumeric display 25 may also be provided onthe device to provide the user with a variety of information concerningdevice and/or treatment status.

In operation, the electrodes 18 a and 18 b are placed in contact withthe patient's skin or mucosa, and electrical energy is delivered to theelectrodes 18 a and 18 b when the device is turned on. As will bedescribed in additional detail below, the treatment protocol typicallyinvolves the application of a series of electrical pulses to theaffected area. In this embodiment, the display 25 may show exhibit acount of the number of treatments applied, thus indicating to the userat any given time how much of the treatment protocol has been completed.

FIG. 2 illustrates the circuitry provided inside the housing 12 of someadvantageous embodiments of the invention. The device will generallyinclude a battery 16, which may be rechargeable or disposable, coupledto a logic/processor circuit 14, a signal generator circuit 17, and thedisplay. 25. The logic/processor circuit 14 drives the display 25 andconfigures the signal generator circuit 17 to output the desiredelectrical signal to the electrodes 18 a and 18 b. Although shown asseparate blocks in FIG. 2, it will be appreciated that thelogic/processor circuit 14 and the signal generator circuit 17 may befunctionally combined, and will typically reside on a common printedcircuit board in the housing 12. The types of signals produced by thesignal generator circuit 17 in advantageous embodiments of the inventionwill be described in additional detail below.

The physical size and shape of the device will advantageously varydepending on the specific intended application. The embodimentillustrated in FIG. 1, for example, is advantageously sized for use onthe legs and genital area. In this embodiment, the electricalstimulation device 10 is approximately 2-3 inches long, approximately1-1.5 inches wide, and approximately 0.5-1 inches deep. As noted above,the device 10 is sized so as to fit comfortably in the hand of the user.The circuit traces forming the concentric electrodes 18 a, 18 b shown inFIG. 1 are approximately 2-3 mm in width, and are plated to a thicknessof less than 1 mm. As illustrated in FIG. 3, in an alternativeembodiment of the genital appplicator, the end of the device 10 whichmounts the electrodes is curved so that it is easier to produce contactbetween the skin of the patient and the entire electrode surface.

Turning now to FIG. 4, there is illustrated another embodiment of theelectrical stimulation device 10. The device 10 includes a housing 12and concentric electrodes 18 a and 18 b at the top end of the device 10.Here, the electrodes 18 a and 18 b are circular, and the centerelectrode 18 b forms a circular pad rather than a ring. This embodimentis adapted for oral application, and advantageously measures about 0.5to 0.75 inches in diameter with a length of about 2 inches. This isabout the same size and shape of a lipstick or lip balm applicator, andthus is very convenient for carrying in a pocket or purse. In thisembodiment, the display 25 may be provided on the bottom flat surfaceopposite the electrode surface. A cap 22 is also preferably provided forthe embodiments of FIGS. 1, 3, and 4. This cap 22 fits over the top endof the device 10 where the electrodes 18 a and 18 b are located. The cap22 acts to protect the electrodes 18 a and 18 b after cleaning withalcohol or hydrogen peroxide and not in use.

In FIGS. 5A, 5B, 6A and 6B there is shown still other embodiments of theelectrical stimulation device 10 of the present invention. In theseembodiments, The device 10 includes a disposable electrode cartridge 24which includes the battery and concentric electrodes 18 a and 18 blocated on the contact head 26 of the device 10, which is located at thedistal end 30 of the device 10. The contact head 26 can be flat (FIGS.5A and 5B) or hemispherical in shape (FIGS. 6A and 6B). The disposableelectrode cartridge 24 snaps into the housing 12, but can be easilyremoved for disposal. As shown in FIG. 5C, the concentric electrodes 18a, 18 b, can be circular; alternatively, as shown in FIG. 6C, theelectrodes 18 a, 18 b can be positioned side-by-side, each electrodecomprising approximately half of a hemispherical surface, separated by astrip of insulating material 26 along an equatorial line of thehemisphere. This embodiment is advantageous in that the electrodes canbe removed and replaced without discarding the entire unit 10.

The devices described above are used by applying the electrodes to thesurface of the affected skin or mucosa and delivering electrical energyto the affected area. It has been found advantageous for a totaltreatment protocol to comprise a series of electrical pulses, withdifferent pulses being different in signal characteristics. The pulsesmay differ in one or more of amplitude, frequency, signal type, e.g. ACor DC or any other electrical signal characteristic. It is hypothesizedthat the different electrical signal characteristics produce differentdisruptive effects on the virus, thus preventing the survival of thoseviruses which may already be or which may become resistant to any oneform of electrical stimulation.

This form of treatment protocol is illustrated in FIG. 7, and isinitiated at start block 30. At block 32, an electrical signal pulse isapplied. At decision block 34, it is determined whether or not the pulsejust applied is the last pulse of the treatment. If not, the systemmoves to block 36, where the device is configured to output a pulsehaving characteristics different from the previous pulse. Looping backto block 32, the pulse having the new desired characteristics isapplied. This process continues until the last pulse of the treatment isapplied, and the treatment then ends at stop block 38.

As mentioned above, the pulses may differ in any one or more of avariety of characteristics. The pulses may change in maximum voltage orcurrent amplitude. The pulses may change between AC waveforms and DCwaveforms. AC pulses may vary in frequency or waveform such as trianglewaves, square waves, or sine waves. As described below, in someadvantageous embodiments, the pulses vary in maximum amplitude fromapproximately 3 volts to approximately 20 volts, and vary in frequencyfrom DC to about 10 kHz.

Two different specific protocols based on the principles described abovehave been devised. Protocol 1 involves ten 30 second applications ofelectrical energy, with a one hour break between each one, wherein each30 second segment is itself divided into sub-segments, which in thisembodiment may be 5, 1, and/or 0.2 second intervals. This treatmentprotocol is defined as follows:

If the ten applications are designated numbers 1 through 10,applications 1, 3, 5, 7, and 9 are as follows:

TABLE 1 5 seconds at 9 VDC 1 second each at 5, 10, 25, 50, and 75 Hz, at9 VAC peak. 5 seconds at 9 VDC 1 second each at 100, 200, 300, 400, and500 Hz, at 9 VAC peak. 5 seconds at 9 VDC 1 second each at 500, 300,100, 50, and 5 Hz, at 9 VAC peak.

Applications 2, 4, 6, 8 and 10 are as follows, all at 9 VAC peak:

TABLE 2 25 step frequency sweep from 5 Hz to 1000 Hz, 0.2 seconds ateach frequency, 9 VAC 25 step frequency sweep from 1000 Hz to 5 Hz, 0.2seconds at each frequency 25 step frequency sweep from 5 Hz to 1000 Hz,0.2 seconds at each frequency 25 step frequency sweep from 1000 Hz to 5Hz, 0.2 seconds at each frequency 25 step frequency sweep from 5 Hz to1000 Hz, 0.2 seconds at each frequency 25 step frequency sweep from 1000Hz to 5 Hz, 0.2 seconds at each frequency

In the above described protocol, the peak voltage remains constant atabout 9 V. A more complex protocol, referred to herein as Protocol 2,has also been developed which includes variation in peak voltage as wellas variations in waveform and frequency. In this specific protocol,nineteen different pulses that have been found useful and are set forthbelow in Tables 3 and 4. Twelve of the pulses are AC waveforms, andseven of the pulses are DC waveforms. Table 5 sets forth 10 differentpulse sequences which are applied in various combinations to theaffected area during a treatment protocol.

TABLE 3 1st 2nd 3rd 4th 5th 6th 7th 8th 9th second second second secondsecond second second second second A1 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz A2 25step sweep from 5 Hz to 1 kHz A3 1 kHz  2 kHz  3 kHz  4 kHz  5 kHz A4 25step sweep from 1 kHz to 5 Hz A5 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz 100 Hz A61 kHz  2 kHz  3 kHz  4 kHz  5 kHz  7 kHz A7 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz100 Hz 125 Hz A8 1 kHz  2 kHz  3 kHz  4 kHz  5 kHz  7 kHz  9 kHz A9 25step sweep from 10 Hz to 2.5 kHz A10 25 step sweep from 2.5 kHz to 10 HzA11 5 Hz 10 Hz 25 Hz 50 Hz 75 Hz 100 Hz 125 Hz 150 Hz 200 Hz A12 1 kHz 2 kHz  3 kHz  4 kHz  5 kHz  7 kHz  9 kHz  10 kHz

TABLE 4 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th second secondsecond second second second second second second second second D1 3 V 4V 5 V 7 V 9 V D2 3 V 4 V 5 V 7 V 9 V 11 V D3 3 V 4 V 5 V 7 V 9 V 11 V 13V D4 3 V 4 V 5 V 7 V 9 V 11 V 13 V 15 V D5 3 V 4 V 5 V 7 V 9 V 11 V 13 V15 V 17 V D6 3 V 4 V 5 V 7 V 9 V 11 V 13 V 15 V 17 V 19 V D7 3 V 4 V 5 V7 V 9 V 11 V 13 V 15 V 17 V 19 V 20 V

TABLE 5 PULSE SEQUENCE 1 A1 D1 A2 D1 A3 D1 A4 2 A1 D1 A2 D1 A3 D1 A4 A13 A1 D1 A2 D1 A3 D1 A4 D1 A1 4 A1 D1 A2 D1 A3 D1 A4 D1 A1 D1 5 A1 D2 A2D2 A3 D2 A4 D2 A1 D2 A2 6 A1 D3 A2 D3 A3 D3 A4 D3 A1 D3 A2 D3 7 A1 D4 A2D4 A3 D4 A4 D4 A1 D4 A2 D4 A3 8 A5 D5 A9 D5 A6 D5 A10 D5 A5 D5 A9 D5 A6D5 9 A7 D6 A9 D6 A8 D6 A10 D6 A7 D6 A9 D6 A8 D6 A10 10 A11 D7 A9 D7 A12D7 A10 D7 A11 D7 A9 D7 A12 D7 A10 D7

Treatment 1

Sequence 1 at 3V

hour break

Sequence 1 at 5V

hour break

Sequence 1 at 7V

hour break

Sequence 1 at 9V

hour break

Sequence 1 at 11V

Treatment 2

Sequence 1 through 10 at 3V

hour break

Sequence 1 through 10 at 5V

hour break

Sequence 1 through 10 at 7V

hour break

Sequence 1 through 10 at 9V

hour break.

Sequence 1 through 10 at 11V

Treatment 3

Sequence 1 through 10 at 3V

hour break

Sequence 1 through 10 at 5V

hour break

Sequence 1 through 10 at 7V

hour break

Sequence 1 through 10 at 9V

hour break

Sequence 1 through 10 at 11V

hour break

Sequence 1 through 10 at 13V

hour break

Sequence 1 through 10 at 15V

hour break

Sequence 1 through 10 at 17V

hour break

Sequence 1 through 10 at 19V

hour break

Sequence 1 through 10 at 20V

Treatment 4

Sequence 1, 3V

Sequence 2, 5V

Sequence 3, 7V

Sequence 4, 9V

Sequence 5, 11V

Sequence 6, 13V

Sequence 7, 15V

Sequence 8, 17V

Sequence 9, 19V

Sequence 10, 20V

Repeat 10 times with one hour break between each repetition.

In these treatment sequences, the peak AC and DC voltages are specified.Thus, in the case of the application of a DC pulse, the maximum voltageapplied will be limited by either the maximum specified in Table 4, orby the maximum specified by the particular treatment segment beingapplied. Thus, If D7 is being applied at 7 V, the pulse applied is onesecond at 3V, one second at 4V, one second at 5V, and eight seconds at7V. However, if D7 is being applied at 20V, the pulse applied is onesecond each at 3V, 4V, 5V, 7V, 9V, 11V, 13V, 15V, 17V, 19V, and 20V. IfD1 is applied at 20 V, the pulse is one second at 3V, one second at 4V,one second at 5V, one second at 7V, and one second at 9V. All AC pulseshave peak voltages as specified by the treatment segment being applied.

Treatment should be begun as soon as possible after the onset ofsymptoms, preferably in the prodromal stage when the characteristictingling, itching or burning sensation is felt. The distal end of thedevice is held to the affected skin or mucosa where symptoms areperceived, and treatment is commenced by pressing the “on” button. Adesignated treatment cycle of about 30 to 60 seconds is automaticallyinitiated. The LED illuminates during this on cycle.

The user generally will not feel any sensation during treatment. By theend of the 10×30 second consecutive treatments of Protocol 1, or by theend of Treatment 1 of Protocol 2, prodromal symptoms should cease. Ifsymptoms continue, or if lesions occur or are still present, it isrecommended that treatment be continued. Under protocol 1, this wouldinvolve a second course of 10 consecutive 30 second treatments. UnderProtocol 2, Treatment 2 as defined above should be administered. If,after this second course of treatments, symptoms or lesions appear orpersist, a third course of ten treatments should be carried out underProtocol 1, or Treatment 3 of Protocol 2 should be applied. Finally, ifsymptoms still remain, Protocol 2 calls for the application of Treatment4 as defined above.

It will be appreciated that a wide variety of treatment protocols couldbe devised based on the principles of the invention, and that the twodescribed above are only two specific examples of treatment protocolswith the advantageous feature of pulse variability.

A number of device electrode placement protocols can be employed withthe present invention and these involve various anatomical sites.Electrode placement sites may be in relationship to neural ganglia whereviruses establish residence. For example, the trigeminal ganglion nearthe ear is a site where HSV-1 (herpes labialis) establishes residence,from which it recurs on the lower lip or face. Therefore this site isideal for electrode placement and is located in front of the ear(external auditory meatus), below the zygomatic arch, and over theposition of the facial nerve and parotid gland. Another neural ganglionexample for electrode placement is the sacral ganglion at the base ofthe spine. This is where HSV-2 (genital herpes) sets up residence fromwhich it recurs in the genital area.

Other electrode placement sites can be in relationship to regional lymphnodes. Examples of these sites would be in the cervical chain of lymphnodes positioned bilaterally at the front of the neck, lymph nodes inthe tonsil bed positioned just under the angle of the jaw (junction ofhorizontal and ascending ramus of mandible), in the axillary chain oflymph nodes positioned under the arms, and in the inguinal lymph nodespositioned bilaterally in the groin.

Further sites for electrode placement can be in relationship to airsinuses such as those in the facial bones of the skull. Examples includethe maxillary antrum positioned below the eyes and above the upperteeth, accessed by placement either side of the nose level with theeyes, and the frontal sinus positioned either side of the midline on theforehead just above the eyes.

With the treatment of viral diseases that affect the whole body, and forserious and life threatening viral diseases such as HIV and AIDS, itwill be necessary to carry out treatments using placements of theelectrical device in other additional anatomical regions using aconsecutive pattern of treatments.

In one such protocol, the device is used consecutively on threedifferent anatomical regions of the body. These three sites are referredto collectively as “The Central Location.” In this, the first placementsite is in the center of the spine, slightly above the level of theshoulders, which is the position of cervical vertebra #7, referred to asC7. The second site is also positioned longitudinally in the center ofthe spine but between the neck and the base of the spine, which is atabout thoracic vertebra #7 (T7). The third and last position is also inthe center of the spine but positioned at the base of the lumbar spineequivalent with the 5th lumbar vertebra, referred to as L5.

In another protocol, a further seven anatomical placement sites areemployed in addition to the above three sites of The Central Location.Whereas the three previous sites are on the back, or dorsal position, ofthe body, the seven additional sites are located on the front, orventral position, of the body. These seven different anatomical regionsof the body coincide with the seven “chakras” and channels of energy.Many workers have contemplated that in addition to a network of nervesand sensory organs, there also exists a subtle system of channels andcenters of energy (chakras) which affects the physical, intellectual,emotional and spiritual being. These seven regions are used as electrodeplacement sites and are positioned in seven specific regions of the bodyranging from the crown to the sternum, including regions such as theheart. The seven regions are generally referred to as the crown, root,sacral, solar plexus, heart, throat, and third eye chakras. These sevenlocations physically correspond to the locations of the top of the head,between the anus and the genitals, between the navel and the genitals,between the navel and the base of the sternum, in the center of thechest, centrally at the base of the throat, and above and between theeyebrows respectively.

In these two final protocol examples of treating viral infections of theentire body, the treatment sequences shown in Table 5, and in Treatment4, are employed whereby ten different pulse sequences are applied invarious combinations. Each of the ten separate outputs ramp upconsecutively through the various voltage levels resulting in a totaltreatment time of eight minutes and forty-five seconds in eachanatomical site. This regimen may be carried out on each of either thethree regions in The Central Location or, additionally, the seven chakraregions as described above, making ten anatomical sites in all.

The three Central Location sites would give a total treatment time of3×8 minutes and 45 seconds, which is 26 minutes and 15 seconds. Theseven chakra regions would give a total treatment time of sixty-oneminutes and fifteen seconds. Treatment of all ten locations would give atotal treatment time of 87 minutes and thirty seconds. The entiresequence would then be repeated according to the protocol employed whichcould be, for example, nine repetitions, which is ten treatments in all.

Use of a stimulation device in the treatment of various forms of viralinfections are further described in the following specific examples.

Example 1 Oral Herpes

A female subject, date of birth Mar. 15, 1975, had a twelve year historyof oral herpes infections. Outbreaks tended to occur at the lip borders,especially the lower lip, and were more frequent during cold weather andduring times of stress. She reported approximately four to six outbreaksper year, each lasting about 10-12 days. Previous treatments had beenunsuccessful.

The subject was given an electrical stimulation device as describedabove that was configured to apply Protocol 1 as described above. Shewas instructed to apply the device directly to the infected area orareas, and apply the ten 30 second treatments as described in Protocol 1above, with a one hour break between each 30 second treatment. Thedevice was configured to automatically step through the ten differentelectrical pulses as shown above as the subject applied the device forthe ten consecutive 30 second periods. Thus, the subject only had toplace the electrodes on the affected area, press the ON button, and waitfor an LED display to turn off after 30 seconds.

After the first treatment, the subject reported that the small vesiclesthat had begun to develop started to dry up immediately after treatment.The small reddish areas indicating the onset of an outbreak disappearedcompletely within three days, as did any symptoms of burning or itching.

Example 2 Recurrent Genital Herpes

The male subject, date of birth Dec. 25, 1955, had a history of genitalherpes for the past 20 years. The outbreaks always occurred on his penisand varied from minor outbreaks to major ones. The subject reported thathe had four outbreaks on average each year. He also reported that in hisopinion, they often occurred in relation to stress and when he wasworking very hard physically.

The subject had an outbreak which was preceded by prodrome symptoms. Thesubject reported that his thighs began to tingle and feel “funny”, whichis what usually happened just before an outbreak. The day following theprodrome symptoms, the subject noticed a small raised red lump on thetop of the head of his penis. The subject started treatment with thedevice of the present invention on the red spot once every hour for atotal of ten treatments using Protocol 1 as described above and as inExample 1. The subject reported that the red spot did not get any largerlike it usually did, and was not painful, also atypical since it usuallywas very painful by the second day. The subject reported that the redspot did not progress to the blister stage. This was the first time inhis twenty-year history of having genital herpes that an outbreak didnot progress to a blister stage. The subject also reported that therewas no release of fluid which was also unusual. The outbreak dried upand disappeared completely after the third day.

The subject had another prodrome stage where the symptoms were similarto those described previously; his thighs started to tingle and burn.The subject noticed that a small outbreak had developed on the undersideof his penis and appeared as a raised red spot. This became larger andthe subject reported that this had all of the signs of being one of hismajor outbreaks that he got regularly about once a year. The subjectstarted using the device for treatment as soon as he noticed theoutbreak. He used the device every hour as instructed, positioning thetip of the device on the red raised lesion, in the same manner asdescribed above. The lesion did not get any larger once treatmentstarted. The subject reported that after the appearance of the red spotand commencement of treatment, there was no formation of blisters, nowetness or oozing of fluid, and no pain. The subject reported that theoutbreak started to resolve itself the day after commencing treatmentwith the device.

Seven months later, the subject reported that he noticed a little redcolored spot appear on the upper side of his penis which swelled anddeveloped into a small bump. The subject reported that there were nosigns of a prodrome stage this time. He used the viral device with thesame treatment regimen of once an hour, and during treatments, the smallbump did not get any larger, and disappeared after a couple of days. Thesubject reported that this was the “best” outbreak he had in the lasttwenty years because there was no pain, no swelling, and no discharge,and it was all over in a couple of days.

Three months later, the subject reported that he had a very smalloutbreak on the left rear thigh. It appeared as a small red spot butthere was no evidence of any lesion on his penis. He used the viraldevice on top of the lesion employing the same protocol as describedabove, and the small lesion did not get any bigger. The subject reportedthat there was no blistering, no discharge and no pain. The outbreakcleared up completely in a couple of days.

Five months later, the subject reported the appearance of a small redswelling on the side of his penis. As soon as he saw evidence of theoutbreak he started treatment with the device using the once-an-hourprotocol described above. The lesion did not progress in size, did notblister, and was not painful. It responded well to the treatment and thelesion disappeared by day three.

Example 3 Human Papiloma Virus

A female subject, date of birth Jun. 21, 1951, had a history of lesionsappearing on the lower part of her legs, generally on the front aspectbetween the knee and the ankle. An outbreak usually consisted of 2-3 tosix or more lesions, and tended to occur during times of stress. Thelesions would become larger over a period of five to seven days, andwould dry up and disappear two to three weeks after their appearance.The lesions were diagnosed as being caused by Human Papiloma Virus, forwhich oral medication and topical cream was prescribed. These treatmentswere not successful.

The subject then tried the electrical stimulation device of the presentinvention, using it directly on the lesions for ten 30 second treatmentsas described above in Examples 1 and 2. She treated each lesionseparately, unless two were very close together, in which case theelectrodes were placed between the two lesions.

The subject reported that the pain subsided immediately, and that thelesions healed and disappeared within three days.

Example 4 Verruca

A male subject, date of birth May 28, 1949, developed a verruca wart onthe sole of his right foot. The lesion was positioned at the front andin the center of the planter surface of the foot immediately to the sideof the large toe prominence. It interfered with the subject's walkingand running. The subject had tried a number of treatments, including 40%salicylic acid pads, but these did not eliminate the wart or theassociated pain and discomfort.

The subject used the stimulation device described above for ten 30second treatments as in Examples 1-3. After the ten treatments, thesubject reported that the pain had stopped completely. The lesion wasstill visible as a raised area on the planter surface of the foot, and asecond series of ten treatments was applied, commencing about one hourafter the conclusion of the first series of ten treatments. By the endof the second course of treatment, the lesion appeared different intexture, was less swollen, and was not painful. The subject was advisedto foot file the region, which he did, after which the affected arealooked normal.

Follow up with the subject over nine months following treatment revealedthat he was completely pain free, with no evidence that the verruca hadreturned.

Thus, the method and device described herein were found to be effectivein the treatment of viral infection. The treatment with the device notonly improved recovery time, but also reduced the frequency ofrecurrence.

The foregoing description details certain embodiments of the invention.It will be appreciated, however, that no matter how detailed theforegoing appears in text, the invention can be practiced in many ways.As is also stated above, it should be noted that the use of particularterminology when describing certain features or aspects of the inventionshould not be taken to imply that the terminology is being re-definedherein to be restricted to including any specific characteristics of thefeatures or aspects of the invention with which that terminology isassociated. The scope of the invention should therefore be construed inaccordance with the appended claims and any equivalents thereof.

What is claimed is:
 1. An apparatus for applying electrical stimulationto a patient's skin or mucous membrane for treating viral infections,comprising: at least one first electrode; at least one second electrode;and means for outputting a series of electrical pulses through the atleast one first electrode and the at least one second electrode, theseries of electrical pulses comprising AC pulses, each comprising ACwaveforms, and DC pulses, each comprising DC waveforms, the AC pulsesand the DC pulses outputted at different and nonoverlapping periods oftime, the frequency of the AC waveforms varying during the time periodswhen AC pulses are outputted.